Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature, 499(7456):43-9, 2013. 1476-4687 Cancer Genome Atlas Research Network U24 CA143882/CA/NCI NIH HHS/United States U24 CA143866/CA/NCI NIH HHS/United States U54 HG003273/HG/NHGRI NIH HHS/United States R01 HG005690/HG/NHGRI NIH HHS/United States U24 CA143840/CA/NCI NIH HHS/United States U24 CA143843/CA/NCI NIH HHS/United States T32 CA071341/CA/NCI NIH HHS/United States U24 CA143858/CA/NCI NIH HHS/United States U24 CA143848/CA/NCI NIH HHS/United States U54 HG003079/HG/NHGRI NIH HHS/United States T32 CA082088/CA/NCI NIH HHS/United States U24 CA143883/CA/NCI NIH HHS/United States U24 CA143867/CA/NCI NIH HHS/United States UL1 TR000005/TR/NCATS NIH HHS/United States P30 CA016672/CA/NCI NIH HHS/United States U54 HG003067/HG/NHGRI NIH HHS/United States R01 CA068490/CA/NCI NIH HHS/United States K24 CA172355/CA/NCI NIH HHS/United States U24 CA143835/CA/NCI NIH HHS/United States U24 CA143845/CA/NCI NIH HHS/United States U24 CA143799/CA/NCI NIH HHS/United States P30 CA008748/CA/NCI NIH HHS/United States U24 CA144025/CA/NCI NIH HHS/United States Journal Article England 2013/06/25 Nature. 2013 Jul 4;499(7456):43-9. doi: 10.1038/nature12222. Epub 2013 Jun 23.
doi  abstract   bibtex   
Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.
@article{RN6171,
   title = {Comprehensive molecular characterization of clear cell renal cell carcinoma},
   journal = {Nature},
   volume = {499},
   number = {7456},
   pages = {43-9},
   note = {1476-4687
Cancer Genome Atlas Research Network
U24 CA143882/CA/NCI NIH HHS/United States
U24 CA143866/CA/NCI NIH HHS/United States
U54 HG003273/HG/NHGRI NIH HHS/United States
R01 HG005690/HG/NHGRI NIH HHS/United States
U24 CA143840/CA/NCI NIH HHS/United States
U24 CA143843/CA/NCI NIH HHS/United States
T32 CA071341/CA/NCI NIH HHS/United States
U24 CA143858/CA/NCI NIH HHS/United States
U24 CA143848/CA/NCI NIH HHS/United States
U54 HG003079/HG/NHGRI NIH HHS/United States
T32 CA082088/CA/NCI NIH HHS/United States
U24 CA143883/CA/NCI NIH HHS/United States
U24 CA143867/CA/NCI NIH HHS/United States
UL1 TR000005/TR/NCATS NIH HHS/United States
P30 CA016672/CA/NCI NIH HHS/United States
U54 HG003067/HG/NHGRI NIH HHS/United States
R01 CA068490/CA/NCI NIH HHS/United States
K24 CA172355/CA/NCI NIH HHS/United States
U24 CA143835/CA/NCI NIH HHS/United States
U24 CA143845/CA/NCI NIH HHS/United States
U24 CA143799/CA/NCI NIH HHS/United States
P30 CA008748/CA/NCI NIH HHS/United States
U24 CA144025/CA/NCI NIH HHS/United States
Journal Article
England
2013/06/25
Nature. 2013 Jul 4;499(7456):43-9. doi: 10.1038/nature12222. Epub 2013 Jun 23.},
   abstract = {Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.},
   keywords = {AMP-Activated Protein Kinases/metabolism
Acetyl-CoA Carboxylase/metabolism
Carcinoma, Renal Cell/classification/*genetics/*metabolism/pathology
Chromatin/genetics/metabolism
Chromatin Assembly and Disassembly/genetics
Citric Acid Cycle/genetics
DNA Methylation/genetics
DNA Mutational Analysis
Epigenesis, Genetic/genetics
GRB10 Adaptor Protein/genetics
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genome, Human/genetics
Genomics
Histone-Lysine N-Methyltransferase/genetics/metabolism
Humans
Metabolic Networks and Pathways/genetics
MicroRNAs/genetics
Mutation
PTEN Phosphohydrolase/metabolism
Pentose Phosphate Pathway/genetics
Phosphatidylinositol 3-Kinases/metabolism
Proto-Oncogene Proteins c-akt/metabolism
RNA, Neoplasm/analysis/genetics
Signal Transduction/genetics
Survival Analysis},
   ISSN = {0028-0836 (Print)
0028-0836},
   DOI = {10.1038/nature12222},
   year = {2013},
   type = {Journal Article}
}

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